Previous literature has well-established genetic factors as being associated with neuroblastoma(NB).About 1%–2%of NB cases are familial,with 85%of these cases predisposed to mutations in the PHOX2B and ALK genes.The ...Previous literature has well-established genetic factors as being associated with neuroblastoma(NB).About 1%–2%of NB cases are familial,with 85%of these cases predisposed to mutations in the PHOX2B and ALK genes.The genetic basis of sporadic NB has been studied through genome-wide association studies and next-generation sequencing approaches.Particularly,germline variants,as well as copy number variations,confer increased risks of NB,often with effect estimates≥1.5,underscoring the strong genetic contributions to NB.However,the strength of the association varied in non-genetic factors.Some risk factors,such as birth defects,maternal illicit drug use,and early infections,had relatively stronger associations(effect estimates≥1.5 or≤0.67),while some other factors remain inconclusive.This suggests that certain non-genetic factors may play a more prominent role in NB risk,while further research is needed to clarify the impact of others.We synthesized and critically evaluated existing literature on the risk factors of NB to provide an overview,analyze the current state of knowledge,and outline a research path to address the relative contributions of genetic and non-genetic factors in NB.Future epidemiologic studies should incorporate novel methods for measuring genetic and non-genetic factors to comprehensively assess the full extent of factors contributing to NB.Furthermore,the utilization of dried blood spots holds promise to overcome technical and recruitment challenges for future studies.These strategies will contribute to a more holistic understanding of NB etiology and potentially lead to improved prevention strategies.展开更多
Environmental conditions change constantly either by anthropogenic perturbation or naturally across space and time.Often,a change in behavior is the frst response to changing conditions.Behavioral fexibility can poten...Environmental conditions change constantly either by anthropogenic perturbation or naturally across space and time.Often,a change in behavior is the frst response to changing conditions.Behavioral fexibility can potentially improve an organism’s chances to survive and reproduce.Currently,we lack an understanding on the time-scale such behavioral adjustments need,how they actually affect reproduction and survival and whether behavioral adjustments are suffcient in keeping up with changing conditions.We used house mice(Mus musculus)to test whether personality and life-history traits can adjust to an experimentally induced food-switch fexibly in adulthood or by intergenerational plasticity,that is,adjustments only becoming visible in the offspring generation.Mice lived in 6 experimental populations of semi-natural environments either on high or standard quality food for 4 generations.We showed previously that high-quality food induced better conditions and a less risk-prone personality.Here,we tested whether the speed and/or magnitude of adjustment shows condition-dependency and whether adjustments incur ftness effects.Life-history but not personality traits reacted fexibly to a food-switch,primarily by a direct reduction of reproduction and sloweddown growth.Offspring whose parents received a food-switch developed a more active stress-coping personality and gained weight at a slower rate compared with their respective controls.Furthermore,the modulation of most traits was condition-dependent,with animals previously fed with high-quality food showing stronger responses.Our study highlights that life-history and personality traits adjust at different speed toward environmental change,thus,highlighting the importance of the environment and the mode of response for evolutionary models.展开更多
The purpose of the present study is to provide guidelines regarding risk factors that may worsen the Long-QT Syndrome (LQTS), based on available literature. This review evaluates the current knowledge on these risk fa...The purpose of the present study is to provide guidelines regarding risk factors that may worsen the Long-QT Syndrome (LQTS), based on available literature. This review evaluates the current knowledge on these risk factors of acquired LQTS, with an emphasis on non genetic risk factors, including environmental factors. PubMed was searched for literature in English from 1999 to 2011 on the molecular and clinical studies of Long-QT syndrome. We agree, with recent investigations described in the literature, that variety of factors, inherited or environmental, can influence expression of ion channel proteins with impact on repolarization.展开更多
Metabolic engineering-driven microbial cell factories have made great progress in the efficient bioproduction of biochemical and recombinant proteins.However,the low efficiency and robustness of microbial cell factori...Metabolic engineering-driven microbial cell factories have made great progress in the efficient bioproduction of biochemical and recombinant proteins.However,the low efficiency and robustness of microbial cell factories limit their industrial applications.Harnessing microbial heterogeneity contributes to solving this.In this review,the origins of microbial heterogeneity and its effects on biosynthesis are first summarized.Synthetic biologydriven tools and strategies that can be used to improve biosynthesis by increasing and reducing microbial het-erogeneity are then systematically summarized.Next,novel single-cell technologies available for unraveling microbial heterogeneity and facilitating heterogeneity regulation are discussed.Furthermore,a combined workflow of increasing genetic heterogeneity in the strain-building step to help in screening highly productive strains-reducing heterogeneity in the production process to obtain highly robust strains(IHP-RHR)facilitated by single-cell technologies was proposed to obtain highly productive and robust strains by harnessing microbial heterogeneity.Finally,the prospects and future challenges are discussed.展开更多
Precise modulation of mechanoreceptor-mediated signal transduction is crucial for decoding cellular mecha-notransduction mechanisms and programming cell fate.This review provides a comprehensive summary of recent adva...Precise modulation of mechanoreceptor-mediated signal transduction is crucial for decoding cellular mecha-notransduction mechanisms and programming cell fate.This review provides a comprehensive summary of recent advances in engineering synthetic mechanoreceptors,spanning from protein-centric genetic encoding to DNA nanotechnology-based non-genetic reprogramming strategies.Genetic engineering strategies employ pro-tein structure encoding and site-directed mutagenesis to reprogram force-response functions in natural mecha-noreceptors.As a complementary non-genetic approach,DNA nanotechnology leverages its programmability,modularity,and predictable mechanical properties to achieve precise control over receptor functionalities.The flourishing development of DNA mechanosensitive nanodevices has provided a promising synthetic toolkit for manipulating mechanoreceptors,enabling precise control over receptor spatial organization and signal trans-duction.A key innovation is the development of novel DNA-functionalized artificial mechanoreceptors(AMRs),which confer force-responsiveness to naturally non-mechanosensitive receptors without genetic modification,thereby enabling customized mechanotransduction and mechanobiological applications.Collectively,this paradigm shift highlights DNA-based non-genetic receptor engineering as a versatile and powerful toolkit,paving new avenues for mechanobiology research and pioneering force-directed therapeutic strategies in regenerative medicine.展开更多
基金Children’s Cancer Research Fund(Minneapolis,MN)provided fellowship support for Eun Mi Jung’s training
文摘Previous literature has well-established genetic factors as being associated with neuroblastoma(NB).About 1%–2%of NB cases are familial,with 85%of these cases predisposed to mutations in the PHOX2B and ALK genes.The genetic basis of sporadic NB has been studied through genome-wide association studies and next-generation sequencing approaches.Particularly,germline variants,as well as copy number variations,confer increased risks of NB,often with effect estimates≥1.5,underscoring the strong genetic contributions to NB.However,the strength of the association varied in non-genetic factors.Some risk factors,such as birth defects,maternal illicit drug use,and early infections,had relatively stronger associations(effect estimates≥1.5 or≤0.67),while some other factors remain inconclusive.This suggests that certain non-genetic factors may play a more prominent role in NB risk,while further research is needed to clarify the impact of others.We synthesized and critically evaluated existing literature on the risk factors of NB to provide an overview,analyze the current state of knowledge,and outline a research path to address the relative contributions of genetic and non-genetic factors in NB.Future epidemiologic studies should incorporate novel methods for measuring genetic and non-genetic factors to comprehensively assess the full extent of factors contributing to NB.Furthermore,the utilization of dried blood spots holds promise to overcome technical and recruitment challenges for future studies.These strategies will contribute to a more holistic understanding of NB etiology and potentially lead to improved prevention strategies.
文摘Environmental conditions change constantly either by anthropogenic perturbation or naturally across space and time.Often,a change in behavior is the frst response to changing conditions.Behavioral fexibility can potentially improve an organism’s chances to survive and reproduce.Currently,we lack an understanding on the time-scale such behavioral adjustments need,how they actually affect reproduction and survival and whether behavioral adjustments are suffcient in keeping up with changing conditions.We used house mice(Mus musculus)to test whether personality and life-history traits can adjust to an experimentally induced food-switch fexibly in adulthood or by intergenerational plasticity,that is,adjustments only becoming visible in the offspring generation.Mice lived in 6 experimental populations of semi-natural environments either on high or standard quality food for 4 generations.We showed previously that high-quality food induced better conditions and a less risk-prone personality.Here,we tested whether the speed and/or magnitude of adjustment shows condition-dependency and whether adjustments incur ftness effects.Life-history but not personality traits reacted fexibly to a food-switch,primarily by a direct reduction of reproduction and sloweddown growth.Offspring whose parents received a food-switch developed a more active stress-coping personality and gained weight at a slower rate compared with their respective controls.Furthermore,the modulation of most traits was condition-dependent,with animals previously fed with high-quality food showing stronger responses.Our study highlights that life-history and personality traits adjust at different speed toward environmental change,thus,highlighting the importance of the environment and the mode of response for evolutionary models.
文摘The purpose of the present study is to provide guidelines regarding risk factors that may worsen the Long-QT Syndrome (LQTS), based on available literature. This review evaluates the current knowledge on these risk factors of acquired LQTS, with an emphasis on non genetic risk factors, including environmental factors. PubMed was searched for literature in English from 1999 to 2011 on the molecular and clinical studies of Long-QT syndrome. We agree, with recent investigations described in the literature, that variety of factors, inherited or environmental, can influence expression of ion channel proteins with impact on repolarization.
基金supported by the National Science Fund for Excellent Young Scholars(32222069)the National Natural Science Foundation of China(32172349,31930085)+1 种基金the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(32021005)the Jiangsu Basic Research Center for Synthetic Biology(BK20233003).
文摘Metabolic engineering-driven microbial cell factories have made great progress in the efficient bioproduction of biochemical and recombinant proteins.However,the low efficiency and robustness of microbial cell factories limit their industrial applications.Harnessing microbial heterogeneity contributes to solving this.In this review,the origins of microbial heterogeneity and its effects on biosynthesis are first summarized.Synthetic biologydriven tools and strategies that can be used to improve biosynthesis by increasing and reducing microbial het-erogeneity are then systematically summarized.Next,novel single-cell technologies available for unraveling microbial heterogeneity and facilitating heterogeneity regulation are discussed.Furthermore,a combined workflow of increasing genetic heterogeneity in the strain-building step to help in screening highly productive strains-reducing heterogeneity in the production process to obtain highly robust strains(IHP-RHR)facilitated by single-cell technologies was proposed to obtain highly productive and robust strains by harnessing microbial heterogeneity.Finally,the prospects and future challenges are discussed.
基金supported by the National Natural Science Foundation of China(No.22504055).
文摘Precise modulation of mechanoreceptor-mediated signal transduction is crucial for decoding cellular mecha-notransduction mechanisms and programming cell fate.This review provides a comprehensive summary of recent advances in engineering synthetic mechanoreceptors,spanning from protein-centric genetic encoding to DNA nanotechnology-based non-genetic reprogramming strategies.Genetic engineering strategies employ pro-tein structure encoding and site-directed mutagenesis to reprogram force-response functions in natural mecha-noreceptors.As a complementary non-genetic approach,DNA nanotechnology leverages its programmability,modularity,and predictable mechanical properties to achieve precise control over receptor functionalities.The flourishing development of DNA mechanosensitive nanodevices has provided a promising synthetic toolkit for manipulating mechanoreceptors,enabling precise control over receptor spatial organization and signal trans-duction.A key innovation is the development of novel DNA-functionalized artificial mechanoreceptors(AMRs),which confer force-responsiveness to naturally non-mechanosensitive receptors without genetic modification,thereby enabling customized mechanotransduction and mechanobiological applications.Collectively,this paradigm shift highlights DNA-based non-genetic receptor engineering as a versatile and powerful toolkit,paving new avenues for mechanobiology research and pioneering force-directed therapeutic strategies in regenerative medicine.
